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K Kuribayashi

Publications and source records attributed to K Kuribayashi.

At least 145 records · Page 8Linked to original sources
PubMed1985

Effector mechanisms of syngeneic anti-tumour responses in mice. I. Establishment and characterization of an exogenous IL-2-independent cytotoxic T-lymphocyte line specific for radiation-induced leukaemia RL male 1.

A CTL line (CTLL-D4) mediating specific cytolytic activity against radiation-induced leukaemia RL male 1 has been established and maintained on a long-term basis without the addition of exogeneous TCGF. This line was originally selected by the limiting dilution of MLTC cells from RL male 1-immune (BALB/c X C57BL/6) F1-nu/+(CB6F1-nu/+) spleen cells (500 cells/well) in the presence of 5% rat TCGF, 2000 rads-irradiated normal CB6F1-nu/+ spleen cells as the feeder cells, and 10,000 rads-irradiated RL male 1 tumour cells as the stimulator. After expansion only with the feeder and tumour cells, CTLL-D4 shows highly specific cytotoxic activity against RL male 1 by in vitro CMC assay, since cells such as RL male 6, RL female 8, RL female 9, P815, MOPC-315 (H-2d), EL-4 (H-2b) and YAC (H-2a) are not killed. Microcytoxicity assay of this line has revealed that CTLL-D4 comprises three subsets of T lymphocytes (100% Thy-1.2+): 15-25% Lyt-1+23-, 60-75% Lyt-1+23+ and 10-15% Lyt-1-23+. The proliferation of this line seems to depend largely upon the syngeneic MLR-like responsiveness of the Lyt-1+23- subsets of CTLL-D4 to the Ia-positive cells in CB6F1-nu/+ splenic feeder cells, and has been restricted to the H-2d-haplotype of the feeder cells. In spite of the vigorous cell proliferation by coculturing with the feeder cells alone, the cytolytic activity of this line begins to decrease after some 7 days of culture in the absence of the stimulator RL male 1 cells which have no capacity to stimulate by themselves. Thus, by long-term culture of CTLL-D4 with the syngeneic feeder cells alone, a new non-cytolytic line (D4f) was established. Mechanisms enabling the long-term maintenance of CTL activity and subset composition have been discussed in terms of cellular cooperation between the subsets of this line.

Animals↗
PubMed1985

Effector mechanisms of syngeneic anti-tumour responses in mice. II. Cytotoxic T lymphocytes mediate neutralization and rejection of radiation-induced leukaemia RL male 1 in the nude mouse system.

We demonstrated the efficacy of a long-term cultured cytotoxic T-lymphocyte line, CTLL-D4, on tumour growth inhibition using athymic nude mice as recipients. CTLL-D4, specific for a unique surface determinant on a radiation-induced leukaemia RL male 1 of BALB/c origin, was obtained from the limiting dilution culture of MLTC cells performed between spleen cells of a CB6F1-nu/+ mouse immunized in vivo and RL male 1 stimulator cells, and cultured for several months in the absence of added TCGF as described in our preceding paper (Kuribayashi, 1985). The specific inhibition of tumour growth by CTLL-D4 was demonstrated both in Winn-type neutralization assay and in systemic transfer experiments. A subcutaneous inoculation of the mixture of CTLL-D4 and RL male 1 cells resulted in the complete inhibition of tumour growth, even at the effector to tumour cell ratio of 1:1, whereas non-cytolytic D4f, which was self-Ia antigen(s)-reactive, composed entirely of Lyt-1+23- T cells and derived originally from CTLL-D4 but completely lost its cytotoxic activity during culture with the irradiated syngeneic feeder cells alone, had no inhibitory effect at all. In the adoptive transfer studies, the subcutaneously established tumours were rejected by the single i.v. transfer of 2 X 10(7) CTLL-D4 cells into CB6F1-nu/nu mice. However, D4f was ineffective again in this systemic transfer system. When the effect of CTLL-D4 cells on tumour rejection in vivo was compared to that of non-cultured spleen cells hyperimmunized with RL male 1 cells, the former exhibited more rapid rejection in nude mice after i.v. transfer than the latter did, suggesting that CTLL-D4 cells also attack the tumour cells much more effectively as effectors in vivo. Thus, it is conceivable that CTLs are mainly involved in tumour rejection in this adoptive transfer system using RL male 1 tumour cells and athymic nude mice.

Animals↗
PubMed1983

Interleukin 2 induces gamma-interferon production: participation of macrophages and NK-like cells.

Interleukin 2 (IL 2) has been shown to be a potent stimulator of natural killer (NK) cells. In the present studies, partially purified mouse and human IL 2 preparations were also found to induce interferon (IFN) from mouse spleen cells. By the criteria of sensitivity to treatment at pH 2 and failure to be neutralized by a potent anti-alpha, beta IFN serum, the species of IFN produced was of type gamma. Cooperation between two types of cell, a macrophage and an NK-like cell, was required for IFN production by murine spleen cells treated with IL 2. The requirement for macrophages could be replaced with supernatant obtained by incubating macrophages for 24 hr with lymphokine preparations containing IL 2. Interestingly, mature T cells apparently played no role in the process. Furthermore, the beige (bg/bg) mutation, which severely impairs NK cell lytic activity, had no effect on the ability of NK-like cells to participate in IFN production. Cell fractionation experiments revealed no dissociation between the requirements for augmentation of NK cytotoxic activity and for IFN production, and it is concluded that at least a portion of the NK boosting induced by IL 2-containing preparations is mediated through gamma-IFN.

Animals↗